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Biomedical subjects

T R Pieber

Publications and source records attributed to T R Pieber.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue NN304 in comparison to NPH insulin in humans.

NN304 is a long-acting insulin analogue that is acylated with a 14-C-fatty acid chain. Protraction of action of this novel insulin analogue is due not to slow absorption after subcutaneous administration but to reversible binding to albumin. We investigated the pharmacokinetic and pharmacodynamic properties of insulin analogue NN304 (0.3 and 0.6 U/kg) in comparison to NPH insulin (0.3 and 0.6 IU/kg) in 10 healthy volunteers performing a randomised, double-blind, cross-over, placebo-controlled glucose clamp study. During the observation period of 24 hours the areas under the insulin curve for NPH[0.3 IU/kg] vs. NPH[0.6 IU/kg] were 60 vs. 102 nmol min l(-1) (p<0.01) and for insulin analogue NN304[0.3 U/kg] vs. NN304[0.6 U/kg] 490 vs. 932 nmol min l(-1) (p <0.001), suggesting a clear dose-response relationship for both NPH insulin and NN304. The amount of disposed glucose (area under the curve of glucose infusion) differed with statistical significance between the five treatments and was highest with NPH[0.6 IU/kg] (2671 mg/kg) and lowest with placebo (265 mg/kg). However, area under the curve of glucose infusion after treatment with NN304 was only 36% (dose of 0.3 U/kg) and 24% (dose of 0.6 U/kg) of that observed with corresponding doses of NPH insulin. Moreover, increasing dosages of NN304 failed to demonstrate a significant dose-response with regard to the area under the curve of glucose infusion. This study demonstrates that the principle of protracted insulin action of NN304 by reversible binding to albumin is effective in humans albeit at a much lower rate of glucose utilisation when compared to NPH insulin. Thus, in contrast to animal studies NN304 and NPH insulin can not be considered equipotent in humans.

Adult↗
PubMed2000

Measurement of interstitial albumin in human skeletal muscle and adipose tissue by open-flow microperfusion.

The absolute concentration of albumin was measured in the interstitial fluid of subcutaneous adipose tissue and skeletal muscle in six healthy volunteers by combining the method of open-flow microperfusion and the no-net-flux calibration technique. By use of open-flow microperfusion, four macroscopically perforated double lumen catheters were inserted into the tissue regions of interest and constantly perfused. Across the macroscopic perforations of the catheters interstitial fluid was partially recovered in the perfusion fluid. Catheters were perfused with five solutions, each containing different concentrations of albumin. Absolute interstitial albumin concentrations were calculated by applying linear regression analysis to perfusate vs. sampled albumin concentration (no-net-flux calibration technique). Interstitial albumin concentrations were significantly lower (P < 0.0001) in adipose tissue (7.36 g/l; r = 0.99, P < 0.0003; range: 4.3-10.7 g/l) and in skeletal muscle (13.25 g/l; r = 0.99, P < 0.0012; range: 9.7 to 15.7 g/l) compared with the serum concentration (48.9 +/- 0.7 g/l, mean +/- SE, n = 6; range: 46.4-50.4 g/l). Furthermore, interstitial albumin concentrations were significantly higher in skeletal muscle compared with adipose tissue (P < 0.01). The study indicates that open-flow microperfusion allows stable sampling of macromolecules from the interstitial space of peripheral tissue compartments. Moreover, the present data report for the first time in healthy humans in vivo the true albumin concentrations of interstitial fluid of adipose tissue and skeletal muscle.

Adipose Tissue↗
PubMed2000

Efficacy and safety of HOE 901 versus NPH insulin in patients with type 1 diabetes. The European Study Group of HOE 901 in type 1 diabetes.

OBJECTIVE: HOE 901 (Hoechst Marion Roussel, Frankfurt, Germany) is a biosynthetic insulin with a prolonged action. The aim of this study was to compare the effect of the long-acting insulin analog HOE 901 with NPH insulin regarding glycemic control in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 333 type 1 diabetic patients were enrolled in this multinational parallel group trial. Subjects were randomized either to two different formulations of HOE 901 (the formulations differed only in zinc content) or to NPH insulin. The study was only partially blinded because patients can distinguish HOE 901 (a clear solution) from NPH (a cloudy suspension). In addition to premeal injections of regular insulin, patients received HOE 901 at bedtime or NPH once daily at bedtime or twice daily in the morning and at bedtime. RESULTS: Fasting plasma glucose levels were significantly lower with HOE 901 (-1.88 mmol/l. P = 0.0005) as were fasting self-monitored blood glucose levels (-0.80 mmol/l, P = 0.0020). HbA1c levels also showed a significant reduction with HOE 901 (-0.14%) versus NPH (P = 0.030). The overall frequency of hypoglycemia did not differ, but the frequency of nocturnal hypoglycemia was significantly (P = 0.0037) lower with HOE 901 (36 vs. 55%). However, this effect on nocturnal hypoglycemia was significant only versus NPH once daily not NPH twice daily. The pattern of adverse events and injection site reactions with HOE 901 was similar to that with NPH. CONCLUSIONS: This study indicates that HOE 901 achieves better control of fasting glucose and HbA1c levels over 4 weeks, and HOE 901 has a possible safety benefit in terms of nocturnal hypoglycemia.

Adult↗
PubMed1999

Pressor and mesenteric arterial hyporesponsiveness to angiotensin II is an early event in haemorrhagic hypotension in anaesthetised rats.

OBJECTIVE: Vascular responsiveness to vasoconstrictors is known to be attenuated in haemorrhagic shock. In this study we assessed the temporal development and the underlying mechanisms of haemorrhage-induced vascular hyporeactivity to pressor agents. METHODS: In phenobarbital-anaesthetised rats hypotension was induced by graded haemorrhage (8 ml blood total). Sham-manipulated rats served as controls. Blood flow (BF) was recorded with ultrasonic transit time flow probes. RESULTS: Following haemorrhage mean arterial pressure (MAP) fell by 25-45 mm Hg and was accompanied by a reduction in mesenteric BF without any alteration of mesenteric vascular conductance (VC). While pressor responses to arginine vasopressin remained unaltered, hyporesponsiveness to phenylephrine (10 nmol kg-1) developed 120-180 min after hypotension had been induced. Pressor and mesenteric constrictor responses to angiotensin II (30 pmol kg-1) became significantly blunted as early as 60 min post haemorrhage. The hypotensive effect of an angiotensin1 receptor antagonist, telmisartan (1 mg kg-1), was likewise blunted 3 h after haemorrhage. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg kg-1) exaggerated the hypotensive reaction to haemorrhage but did not prevent the development of angiotensin II hyporesponsiveness. In contrast, the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (10 mg kg-1), as investigated 3 h post haemorrhage, restored the systemic pressor responses to angiotensin II and phenylephrine as well as the mesenteric constrictor responses to phenylephrine to normal level and diminished the mesenteric hyporesponsiveness to angiotensin II. Glibenclamide (20 mg kg-1), an inhibitor of ATP-sensitive K- channels given 180 min post haemorrhage, partially reversed haemorrhage-induced hypotension but did not modify angiotensin II hyporesponsiveness. CONCLUSION: Systemic pressor responsiveness and mesenteric arterial reactivity to endogenous and exogenous angiotensin II is selectively impaired at an early stage of haemorrhagic hypotension. This phenomenon partially involves NO and is not related to ATP-sensitive K+ channels.

Angiotensin II↗
PubMed1999

Direct access to interstitial fluid in adipose tissue in humans by use of open-flow microperfusion.

To gain direct access to the interstitial fluid (ISF), a new technique called open-flow microperfusion has been evaluated. This method is based on a double-lumen catheter with macroscopic (0.3-0.5 mm diameter) perforations that is inserted into the subcutaneous adipose tissue and constantly perfused. Thus partial equilibration between the ISF and the perfusion fluid occurs. The glucose concentration of the ISF was determined by established (zero flow rate, no net flux, and recirculation procedures) and new (ionic reference and suction technique) calibration methods by use of open-flow microperfusion. The data show that 1) the glucose concentration in the ISF is significantly lower than the corresponding arterialized venous plasma values during basal steady-state conditions (adipose tissue 3.2 +/- 0.10 mM, plasma 5.27 +/- 0.12 mM) as well as during hyperglycemic clamp experiments (adipose tissue 7.3 +/- 0.13 mM, plasma 9.91 +/- 0.16 mM), and 2) it is possible to determine the recovery continuously by using the ion concentration of the ISF as an internal standard (ionic reference).

Adipose Tissue↗
PubMed1999

Combined treatment of metastatic osteosarcoma of the spine.

We report on a 28-year-old male with a single metastasis of an osteosarcoma in the twelfth thoracic vertebra occurring 9 years after initial diagnosis of the primary tumour in the left distal femur and neoadjuvant treatment according to a modified T-10 protocol. After pre-operative second-line combination chemotherapy with doxorubicin, carboplatin and etoposide leading to regression of the primarily inoperable metastasis wide resection of the tumour employing total spondylectomy was done. The duration of response had been 65 months since the end of subsequent postoperative chemotherapy with the same regimen.

Adult↗
PubMed1999

Plasma and interstitial glucose dynamics after intravenous glucose injection: evaluation of the single-compartment glucose distribution assumption in the minimal models.

Recent experimental evidence suggests that estimates of glucose effectiveness (S(G)) from the minimal model of unlabeled glucose disappearance (Cold-MM) are in error. The single-compartment glucose distribution assumption embedded in the model has been indicated as a possible source of error. In this study, to directly examine the single-compartment assumption, we measured plasma and interstitial glucose concentrations after intravenous glucose injection. Additionally, we compared the accuracy of the estimates of glucose effectiveness from the Cold-MM and the single-compartment tracer minimal model (Hot-MM). Paired labeled intravenous glucose tolerance tests (IVGTTs) were performed in each of six C-peptide-negative type 1 diabetic subjects. Two different insulin infusion protocols were used: an infusion at constant basal rates and an infusion at variable rates to mimic a normal insulin response. During the labeled IVGTT with basal insulin infusion, the microperfusion technique was employed to sample adipose tissue interstitial fluid. Marked differences between the plasma and interstitial dynamics of (cold) glucose were observed during the first 22 min after glucose injection. These results suggest that the requirements for a single-compartment representation of glucose kinetics are not satisfied during at least the first 22 min of an IVGTT. Data from the labeled IVGTT with normal insulin response were used to identify the minimal-model parameters. The measure of S(G) derived using the Cold-MM was 3.44-fold higher than the direct measure obtained from the labeled IVGTT with basal insulin infusion (0.0179+/-0.0027 vs. 0.0052+/-0.0010 min(-1), P<0.01). The measure of glucose effectiveness (S(G)*) derived by the Hot-MM was 1.36-fold higher than the direct measure available from the labeled IVGTT with basal insulin infusion (0.0079+/-0.0013 vs. 0.0058+/-0.0004 min(-1), P>0.26). These results suggest that the Hot-MM is more appropriate for the evaluation of glucose effectiveness than the Cold-MM.

Adult↗
PubMed1998

Novel system for real-time ex vivo lactate monitoring in human whole blood.

The objective of the study was to evaluate the performance of an amperometric enzyme based lactate sensor and to investigate the possibility of replacing a double lumen catheter based blood withdrawal system with a heparin coated single lumen system. The inner lumen of a double lumen catheter which was placed in a peripheral vein was perfused with heparin solution. The outer lumen was used to collect heparinized blood samples at a defined flow rate. The single lumen system was attached to a heparinized catheter which was also placed in a peripheral vein. The undiluted blood samples were collected at a specified flow rate. A sensor flow chamber incorporating an amperometric thin-film lactate microbiosensor was placed in the sampling line for real-time lactate monitoring. Plasma lactate concentrations were measured during frequently performed hyperlactatemia bicycle ergometer experiments in six healthy volunteers (age 25.8 +/- 2.8 years, BMI 22.7 +/- 1 kg/m2). Additionally, plasma lactate was measured in real-time using the lactate sensors. The first three experiments were performed with a double lumen based catheter system whereas the following three experiments were performed with a heparin coated catheter system. The correlation coefficients of sensor readings and laboratory analyzer results in all six experiments were between 0.93 and 0.99, respectively (P < 0.001). The miniaturized lactate sensors showed a linear range up to 25 mmol/l lactate concentration and 95% response times < 30 s in undiluted serum. During the experiments maximum lactate concentrations of 14 mmol/l were achieved. Improvements of system performance using heparin coated catheter systems could be shown. The overall SD of the sensor readings compared to laboratory results using three double lumen catheter based systems was 0.91 mmol/l whereas the SD using three heparin coated systems was 0.65 mmol/l. In summary, real-time monitoring of lactate in human whole blood is feasible with such a device and can be improved by using heparin coated catheter systems.

Adult↗
PubMed1998

Near fatal anticholinergic intoxication after routine fundoscopy.

We describe a case of severe anticholinergic intoxication following the topical instillation of tropicamide-containing eyedrops. Tropicamide is a short-acting atropine-like derivative and has been regarded as an effective and safe mydriatic. Half an hour after routine fundoscopy, a 62-year-old man experienced two generalized seizures with respiratory arrest and required intubation and mechanical ventilation. The patient was treated with physostigmine and made a full recovery.

Antidotes↗
PubMed1998

Lactate metabolism of subcutaneous adipose tissue studied by open flow microperfusion.

Open flow microperfusion and a novel calibration technique (ionic reference technique) were evaluated for the frequent measurement of the absolute lactate concentration in sc adipose tissue. Furthermore, the influence of the plasma insulin concentration on the lactate concentration of sc adipose tissue was investigated during hyperglycemia. Sixteen lean healthy young men participated in the studies. In the postabsorbtive state the mean sc lactate concentrations were 1.29 and 1.36 mmol/L for the ionic reference technique and the no net flux protocol, respectively (not significant, P > 0.05). The simultaneously measured arterialized plasma lactate concentration was significantly lower at 0.77 mmol/L (P < 0.05). Both the sc lactate concentration (1.8+/-0.33 mmol/L) and the plasma lactate concentration (0.96+/-0.03 mmol/L) were significantly elevated during a hyperinsulinemic euglycemic clamp experiment. During a hyperglycemic clamp experiment the sc lactate concentration reached a significantly elevated plateau (2.15+/-0.27 mmol/L) that was not influenced by the increasing plasma insulin concentration. It is concluded that 1) open flow microperfusion combined with the ionic reference technique enables frequent measurement of the sc lactate concentration; 2) sc adipose tissue is a significant source of lactate release in the postabsorbtive state as well as during hyperinsulinemic clamp conditions; and 3) insulin concentrations greater than 180 pmol/L have no further influence on adipocyte stimulation of sc adipose tissue with respect to lactate release.

Adipose Tissue↗
PubMed1998

Validation of home blood glucose meters with respect to clinical and analytical approaches.

OBJECTIVE: To evaluate the clinical and analytical accuracy of home blood glucose meters. RESEARCH DESIGN AND METHODS: Six blood glucose meters--Reflolux S (Boehringer Mannheim, Mannheim, Germany), One Touch II (LifeScan, Milpitas, CA), Glucocard Memory (Menarini, Florence, Italy), Precision QID (Medisense, Cambridge, U.K.), HaemoCue (HaemoCue, Angelholm, Sweden), and Accutrend alpha (Boehringer Mannheim, Mannheim, Germany)--were compared with a reference method (Beckman Glucose Analyzer II) under controlled conditions (glucose clamp technique). Validation of the blood glucose meters was accomplished by clinically oriented approaches (error grid analysis), statistical approaches (variance components analysis), and by the criteria of the American Diabetes Association (ADA), which recommend a target variability of < 5%. RESULTS: A total of 1,794 blood glucose monitor readings and 299 reference values ranging from 2.2 to 18.2 mmol/l were analyzed (705 readings < 3.89 mmol/l, 839 readings between 3.89 and 9.99 mmol/l, and 250 readings > 9.99 mmol/l). According to error grid analysis, only Reflolux S and Glucocard M had 100% of estimations within the clinically acceptable zones A and B. Assessment of analytical accuracy revealed substantial differences between the glucose meters after separation of the data into defined glycemic ranges. None of the devices met the ADA criteria. CONCLUSIONS: To evaluate accuracy of blood glucose meters, error grid analysis, as well as statistical models, are helpful means and should be performed together. Analytical performance of currently available home blood glucose meters differs substantially within defined glycemic ranges.

Blood Glucose Self-Monitoring↗
PubMed1997

Different influence of CGRP (8-37), an amylin and CGRP antagonist, on the anorectic effects of cholecystokinin and bombesin in diabetic and normal rats.

Because previous studies had suggested that the anorectic effects of cholecystokinin (CCK) and bombesin (BBS) depend partly on the release of amylin or calcitonin gene-related peptide (CGRP), we investigated the influence of the amylin and CGRP receptor antagonist CGRP (8-37) on the anorectic effects of CCK and BBS in streptozotocin (STZ)-diabetic and nondiabetic rats. STZ-diabetic rats had significantly lower plasma amylin and insulin concentrations than nondiabetic control rats. Amylin (5 micrograms/kg or 2.5 micrograms/rat) injected IP at dark onset after 24-h food deprivation elicited an anorectic effect of similar extent in STZ-diabetic and control rats. Under similar conditions, CCK (0.25 and 2 micrograms/kg) and BBS (5 micrograms/kg) reduced food intake in both STZ-diabetic and nondiabetic rats. These effects were markedly attenuated by CGRP (8-37) (10 micrograms/kg) in non-diabetics but not in STZ-diabetic rats. It is concluded that part of the anorectic effects of CCK and BBS depend on the release of amylin from pancreatic B-cells.

Amyloid↗
PubMed1997

Open-flow microperfusion of subcutaneous adipose tissue for on-line continuous ex vivo measurement of glucose concentration.

OBJECTIVE: To evaluate a novel technique for on-line continuous glucose measurement in subcutaneous adipose tissue, and to investigate its accuracy for detection of hypoglycemia. RESEARCH DESIGN AND METHODS: The method combined an open-flow microperfusion of subcutaneous adipose tissue using a double lumen catheter and an extracorporeal sensor cell. An isotonic ion-free solution was perfused through the inner lumen of the catheter, equilibrated with the subcutaneous tissue fluid, and sampled through the outer lumen. The recovery was continuously monitored as the ratio between the measured sampled fluid conductivity and the subcutaneous tissue fluid conductivity (assumed to have a constant value of 1.28 S/m at 25 degrees C). Glucose concentration was calculated on-line from the measured glucose in the sampled fluid and the measured recovery in healthy volunteers during hyperglycemic glucose loads (n = 8), hypoglycemic hyperinsulinemic clamp (n = 6), and a 24-h monitoring period (n = 7). RESULTS: Subcutaneous glucose concentrations in the fasting state were 94% of the plasma glucose concentrations in arterialized venous samples. According to the error grid analysis, 96.9% of the on-line measured subcutaneous glucose concentrations during hyperglycemia and 96.3% during hypoglycemia were in accurate or acceptable zones. The mean differences between the measured subcutaneous glucose and the actual plasma glucose concentration were -0.06-3.3 mmol/l (hyperglycemia), and -0.6-1.1 mmol/l (hypoglycemia). CONCLUSIONS: By combining open-flow microperfusion, glucose sensor, and conductivity measurement, glucose concentration in the subcutaneous adipose tissue can be monitored on-line, extracorporeally, and continuously without any in vivo calibration, and gives accurate measurements during hyper- and hypoglycemia.

Adipose Tissue↗
PubMed1996

[Driver's license, driving habits and traffic safety of patients with diabetes mellitus].

Motoring practices of diabetic drivers are similar to those of the average driving population. Due to the sudden onset of disabling hypoglycemia and the long-term complications of the disease, particularly retinopathy, one might assume that diabetic drivers are more prone to road traffic accidents than the average driver; however, the risk is not increased. The Council of the European Union recently laid down guidelines for dealing with this problem, which will lead to the introduction of a new law in Austria governing driving licensing. This legislation is currently under consideration. We recommend that discrimination between patients requiring therapeutic regimens with potential hypoglycemic side effects (insulin and/or sulphonylureas) and those who are not at risk of hypoglycemia (controlled by diet only or oral antidiabetic drugs other than sulphonylureas) should be legally defined by the licensing authorities. Furthermore, the legal enforcement of participation by diabetic drivers in a structured teaching programme, with the special aim of informing on traffic attitudes and avoidance of hypoglycemia while driving, might be of great importance for safety on the road.

Accidents, Traffic↗
PubMed1996

Accuracy of home blood glucose meters during hypoglycemia.

OBJECTIVE: To evaluate the accuracy of home blood glucose meters during hypoglycemia. METHODS: Six blood glucose meters-One Touch II (LifeScan, Milpitas, CA), Companion II (Medisense, Cambridge, U.K.), Reflolux (Boehringer Mannheim, Mannheim, Germany), Accutrend (Boehringer Mannheim), Elite (Bayer, Munich, Germany), and HemoCue (HemoCue, Angelholm, Sweden)-were compared with a reference method (Beckman Glucose Analyzer 2). Glucose concentrations from arterialized venous blood samples were measured using all glucose meters (whole blood) and the reference method (plasma) during hypoglycemic-hyperinsulinemic clamps in 15 subjects. RESULTS: In total, 663 blood glucose monitor readings and 119 reference values ranging from 2.28 to 3.89 mmol/l were analyzed. The correlation coefficients and the percentage of measurements within 20% and outside 40% of the reference values for each glucose meter were as follows: One Touch II: 0.91, 99.2% and 0%; Companion II: 0.81, 88.2% and 2.5%; Reflolux: 0.78, 85.0% and 0.9%; Accutrend: 0.88, 46.0% and 6.6%; Elite: 0.78, 75.6% and 4.2%; and HemoCue: 0.93, 96.6% and 0% (P < 0.001). CONCLUSIONS: There were substantial differences between the blood glucose meters during hypoglycemia, and none of the devices met the latest criteria recommended by the American Diabetes Association.

Blood Glucose↗